José de Jesús Garduno-Garcia1,2, Amalia Gastaldelli1,3, Ralph A DeFronzo1,2, Raweewan Lertwattanarak1,2, Jens J Holst4, Nicolas Musi1,5,6. 1. Diabetes Division, University of Texas Health Science Center, San Antonio, Texas. 2. Texas Diabetes Institute, San Antonio, Texas. 3. Institute of Clinical Physiology, Pisa, Italy. 4. University of Copenhagen, Copenhagen, Denmark. 5. San Antonio Geriatric Research, Education and Clinical Center, San Antonio, Texas. 6. Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas.
Abstract
Objective: Insulin secretion (IS) declines with age, which increases the risk of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older adults. IS is regulated by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses that incretin release is lower in older adults and that this decline is associated with β-cell dysfunction. Research Design: A total of 40 young (25 ± 3 years) and 53 older (74 ± 7 years) lean nondiabetic subjects underwent a 2-hour oral glucose tolerance test (OGTT). Based on the OGTT, subjects were divided into three groups: young subjects with normal glucose tolerance (Y-NGT; n = 40), older subjects with normal glucose tolerance (O-NGT; n = 32), and older subjects with IGT (O-IGT; n = 21). Main Outcome Measures: Plasma insulin, C-peptide, GLP-1, and GIP concentrations were measured every 15 to 30 minutes. We quantitated insulin sensitivity (Matsuda index) and insulin secretory rate (ISR) by deconvolution of C-peptide with the calculation of β-cell glucose sensitivity. Results: Matsuda index, early phase ISR (0 to 30 minutes), and parameters of β-cell function were lower in O-IGT than in Y-NGT subjects but not in O-NGT subjects. GLP-1 concentrations were elevated in both older groups [GLP-1 area under the curve (AUC)0-120 was 2.8 ± 0.1 in Y-NGT, 3.8 ± 0.5 in O-NGT, and 3.7 ± 0.4 nmol/L∙120 minutes in O-IGT subjects; P < 0.05], whereas GIP secretion was higher in O-NGT than in Y-NGT subjects (GIP AUC0-120 was 4.7 ± 0.3 in Y-NGT, 6.0 ± 0.4 in O-NGT, and 4.8 ± 0.3 nmol/L∙120 minutes in O-IGT subjects; P < 0.05). Conclusions: Aging is associated with an exaggerated GLP-1 secretory response. However, it was not sufficient to increase insulin first-phase release in O-IGT and overcome insulin resistance.
Objective: Insulin secretion (IS) declines with age, which increases the risk of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older adults. IS is regulated by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses that incretin release is lower in older adults and that this decline is associated with β-cell dysfunction. Research Design: A total of 40 young (25 ± 3 years) and 53 older (74 ± 7 years) lean nondiabetic subjects underwent a 2-hour oral glucose tolerance test (OGTT). Based on the OGTT, subjects were divided into three groups: young subjects with normal glucose tolerance (Y-NGT; n = 40), older subjects with normal glucose tolerance (O-NGT; n = 32), and older subjects with IGT (O-IGT; n = 21). Main Outcome Measures: Plasma insulin, C-peptide, GLP-1, and GIP concentrations were measured every 15 to 30 minutes. We quantitated insulin sensitivity (Matsuda index) and insulin secretory rate (ISR) by deconvolution of C-peptide with the calculation of β-cell glucose sensitivity. Results: Matsuda index, early phase ISR (0 to 30 minutes), and parameters of β-cell function were lower in O-IGT than in Y-NGT subjects but not in O-NGT subjects. GLP-1 concentrations were elevated in both older groups [GLP-1 area under the curve (AUC)0-120 was 2.8 ± 0.1 in Y-NGT, 3.8 ± 0.5 in O-NGT, and 3.7 ± 0.4 nmol/L∙120 minutes in O-IGT subjects; P < 0.05], whereas GIP secretion was higher in O-NGT than in Y-NGT subjects (GIP AUC0-120 was 4.7 ± 0.3 in Y-NGT, 6.0 ± 0.4 in O-NGT, and 4.8 ± 0.3 nmol/L∙120 minutes in O-IGT subjects; P < 0.05). Conclusions: Aging is associated with an exaggerated GLP-1 secretory response. However, it was not sufficient to increase insulin first-phase release in O-IGT and overcome insulin resistance.
Authors: J Korosi; C H McIntosh; R A Pederson; H U Demuth; J F Habener; R Gingerich; J M Egan; D Elahi; G S Meneilly Journal: J Gerontol A Biol Sci Med Sci Date: 2001-09 Impact factor: 6.053
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